Clinical Implications of the Expression of TCR and NF-KB Pathway Genes in Nodal Peripheral T-Cell Lymphomas.
Socorro Maria Rodriguez-Pinilla, Maria Encarnacion Casttillo Sanchez, Carmen Gonzalez, Jose Rodriguez, Cristina Gomez-Abad, Lucia Ferrando Lamana, Grevelin Sosa, Jose Carlos Rivero, Javier Menarguez, Isabel Blanco Gomez, Fanny Camacho, Paloma Ramos Guillen, Carlos Perez Seoane Orduna, Carlos Barrionuevo, Manuela Mollejo, Miguel Angel Piris. CNIO, Madrid, Spain; 12 de Octubre Hospital, Madrid, Spain; Alcorcón Hospital, Madrid, Spain; Dr Negrín Hospital, Gran Canaria, Spain; Gregorio Marañón Hospital, Madrid, Spain; General Segovia Hospital, Segovia, Spain; Getafe University Hospital, Madrid, Spain; Príncipe de Asturias University Hospital, Alcalá de Henares,Madrid, Spain; Reina Sofía University Hospital, Córdoba, Spain; INEN, Lima, Peru; Virgen de la SAlud Hospital, Toledo, Spain
Background: Angioimmunoblastic-T-cell lymphoma(AITL) and Peripheral-T-cell lymphoma-not-specified(PTCL-NOS) constitute the most frequent types of Nodal-peripheral-T-cell-lymphoma(NPTCLs). Both carry on an unfavourable prognosis, although specific pathogenetic alterations have not yet been identified. Nevertheless, gene expression studies have identified different signatures for both AITL and PTCL-NOS. The biological and clinical relevance of the expression of CD30 and TCR genes is still under investigation.
Design: A group of 194 consecutive NPTCLs (89 AITL and 105 PTCL-NOS (31 expressing CD30)), were analyzed for the expression of TCR, CD30 and NF-kB markers, using antibodies for CD3, CD30, TCRBF1, TCRGAMMA, EMA, ALK, ZAP70, PD1, EZRIN, MOESIN, CAVEOLIN1, FASCIN, JUNB, BLIMP1, NFKB-P50, NFKB-P52, REL-B, C-REL and P65. Fisher's exact test, Kaplan-Meier survival curves and multivariate Cox regression model were used when appropriate.
Results: None of the cases expressed TCRGAMMA, EMA, ALK, P65 or C-REL. CD3, TCRBF1, CD30, EZRIN, MOESIN, CAV1, FASCIN, ZAP70, NFKBP50, RELB, NFKBP52, PD1, JUNB and BLIMP1 were present in 96.4, 95.7, 11.8, 77.7, 96.7, 12.7, 30.5, 84.5, 8.9, 7.9, 15.3, 67.8, 12.5 and 14.0 per cent of the cases, respectively.
A direct statistical relationship was found between CD3 and TCRBF1 and inverse to the presence of CD30. Moreover, CD3/TCRBF1 positive cases were related to the presence of EZRIN. On the other hand, CD30-positive cases showed NFKB activation,FASCIN, BLIMP1 and JUNB expression.
An increased expression of JUNB and BLIMP1, and the loss of TCRBF1 and EZRIN expression were significant in the univariate analysis for overall survival. Moreover, both IPI and PIT in this series were associated with poor outcome. The multivariate analysis identified the lost of EZRIN and high PIT as independent prognostic factors for survival.
Conclusions: The expression of TCR-signalling pathway molecules seems to be opposed to the expression of CD30 and NF-KB genes in this series. The lost of EZRIN expression is an independent prognostic factor of poor outcome after multivariate analysis.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 227, Tuesday Morning